Schistosomal infections are caused when infected fresh or salt water snails shed free swimming infective larval parasites (cercariae) into the water which infect both animals and humans by the penetration of the parasite through their skin. The penetration of the skin by the parasites can result in infections ranging from skin infection (schistosome cercarial dermatitis or swimmer's itch) to schistosomiasis.
Cases of schistosome cercarial dermatitis have been reported from many regions of the United States, Australia, Europe, Central and South America, Africa, India, New Zealand, Japan, Malaya and Thialand. The schistosomes which are responsible for the major reports of fresh water cercarial dermatitis belong to the genera Trichobilharzia, Ornithobilharzia, and Schistosoma. Microbilharzia spp. cercariae have been identified as the major cause of cercarial dermatitis along salt water beaches of California, Connecticut, Florida, Hawaii, and Rhode Island. Various schistosome species belonging to the genera Schistosomatium, Austrobilharzia, Gigantobilharzia, Heterobilharzia, Orientobilharzia, Ornithobilharzia and Trichobilharzia, as well as Schistosoma and Microbilharzia have been implicated in causing cercarial dermatitis.
Schistosomiasis (also known as bilharziasis, is a state of infection with parasitic flat worms (trematodes) belonging to one or more species of blood flukes of the family Schistosomatidae. Schistosomiasis is the most important among parasitic diseases caused by worms. An estimated 200 million people are infected by blood flukes in regions of Asia, Africa, South America, and also the Caribbean area. The human disease complex results from infection by three major species of digenetic trematodes, viz., Schistosoma mansoni, S. japonicum, and S. haematobium. Other schistosome species, notably Schistosoma mekongi, S. intercalatum, S. bovis, S. rodhaini, S. spindale, S. mattheei, S. margrebowiei, Schistosomatium douthitti and Heterobilharzia americana are also known to establish human infections. Fundamentally, an infected fresh water snail sheds free swimming infective forms (cercariae) into the water, and man (or other animal) is infected by the penetration of the parasite through the skin, followed by maturation of the worms (male and female) in the body, pairing of male and female worms, shedding of eggs in excrement into water; host snails are then invaded by larvae (miracidia) for continuation of the cycle. In the animal host, the schistosomes enter the blood circulation and pass through the lungs to mature in the liver, then reside in mesenteric-portal or pelvic blood circulatory systems. Eggs are laid by the female worm and migrate into the lumen of the small intenstine in the case of Schistosoma japonicum and S. mansoni or the bladder in the case of S. haematobium and, rarely, S. mansoni. Most of the pathological effects resulting from schistosomal infections derive from the spined eggs, both within the body and in being shed in the uninary or fecal stream. Specific primary clinical problems occur in the intestine and bladder, together with seconary ones in liver, spleen, and lungs, plus variable involvement of the central nervous system and retina. The worms may live for many years and the immune response of the host has little effect on established adult schistosomes, but may work against development of new infections. Pathological changes in schistosomiasis are considerably variable with the species and strain of parasite and are influenced by such factors as duration of the infection, intercurrent infections, and nutritional state of the animal host.
Treatment of the schistosomiases does not reverse the damage already done the animal host by the parasite worms. Anti-schistosomal agents generally impair the production of eggs and hinder development and functions of the flukes, with or without actually killing them. "Cure" is said to be achieved when viable eggs are no longer found in the excrement. It should be understood that such criterion does not imply absence of worms. Successful treatment of the schistosomiases is difficult to achieve safely, for anti-schistosomal agents are appreciably toxic to the host. Suppressive management of schistosomiasis through administration of drugs at regular intervals may also be hazardous to the patient. Treatment of the infections is increasingly difficult in the sequence: Schistosoma haematobium, S. mansoni, and S. japonicum. That is essentially the same as the general extent of severity of the consequences of those schistosomes.
Control of schistosomiasis through interruption of the life cycle of the parasite is a more attractive course of action than treatment of the infection. Two points at which control may be exercised are eradication of the snail intermediate host and prevention by protection of the animal host against the cercariae shed by the snails. Various means have been tried to eliminate snails, for example, mollscicides and biological control measures. However, the basic problems have not been solved and even 0.2% of a snail population being infected renders a region highly endemic to schistosomiasis.
The use of a wide variety of topically applied prophylactics to prevent infection by human schistosome cercariae has been comprehensively reviewed by Pellegrino in Experimental Parasitology, Vol. 21, pages 112 to 131 (1967). Since this review, however, only a few topical prophylactic agents have been evaluated by Gilbert et al., in the Journal of Parasitology, Vol. 56, pages 397-398, (1970); Austin and Frappaolo, in the American Journal of Topical Medicine and Hygiene, Vol. 22, pages 743 to 747, (1973); and Greene et al., in the American Journal of Tropical Medicine and Hygiene, Vol. 32, pages 1356 to 1363, (1983). Prior to applicants' invention, the most effective topical cercarial antipenetrants reported by other investigators appear to have been bithionol and hexachlorophene (Kemp et al., Military Medicine, Vol. 119, pages 1 to 10, 1956; and Campbell and Cuckler, American Journal of Tropical Medicine and Hygiene, Vol. 10, pages 712 to 715, 1961).
Niclosamide, for example, and its ethanolamine salt have been widely used as both a molluscicide and a cercaricide to control Schistosoma mansoni when applied to infested waters at concentrations as low as 0.1-0.2 mg/l (Webbe, Bulletin of the World Health Organization, Vol. 25, pages 525 to 531, (1961)). However, there have been no published scientific studies of niclosamide describing its use as a topical antipenetrant. In our study it did not cause any observable dermal reaction, did not discolor the skin, and resisted removal by water washing.